Stabilized formulations containing anti-ngf antibodies

Abstract

The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human nerve growth factor (hNGF). The formulations may contain, in addition to an anti-hNGF antibody, at least one non-ionic surfactant, at least one sugar, and acetate. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.

1 . A pharmaceutical formulation comprising: (i) a human antibody that specifically binds to human nerve growth factor (hNGF); (ii) a non-ionic surfactant; and (iii) a carbohydrate. 
     
     
         2 . The pharmaceutical formulation of  claim 1 , wherein the carbohydrate is a sugar. 
     
     
         3 . The pharmaceutical formulation of  claim 2 , wherein the sugar is selected from the group consisting of sucrose, glucose, mannitol, sorbitol, lactose and trehalose. 
     
     
         4 . The pharmaceutical formulation of  claim 3 , wherein the sugar is sucrose. 
     
     
         5 . The pharmaceutical formulation of  claim 1 , wherein the non-ionic surfactant is selected from the group consisting of polysorbate 20, polysorbate 80 and polyoxyethylene sorbitan monooleate. 
     
     
         6 . The pharmaceutical formulation of  claim 5 , wherein the non-ionic surfactant is polysorbate 20. 
     
     
         7 . The pharmaceutical formulation of  claim 6 , further comprising at least one amino acid selected from the group consisting of histidine or arginine. 
     
     
         8 . The pharmaceutical formulation of  claim 1 , further comprising about 1 mM to about 50 mM acetate. 
     
     
         9 . A pharmaceutical formulation comprising: (i) about 0.1 to 100 mg/mL of a human antibody that specifically binds to hNGF; (ii) about 0.01 to 1.0% of polysorbate 20; and (iii) about 1 to 20% sucrose. 
     
     
         10 . The pharmaceutical formulation of  claim 9  comprising: (i) about 0.2 to 75 mg/mL of a human antibody that specifically binds to hNGF; (ii) about 0.02 to 0.5% polysorbate 20; and (iii) about 5 to 10% sucrose. 
     
     
         11 . The pharmaceutical formulation of  claim 10 , comprising: (i) about 0.6-60 mg/mL of a human antibody that specifically binds to hNGF; (ii) about 0.05% polysorbate 20; and (iii) about 8% sucrose. 
     
     
         12 . The pharmaceutical formulation of  claim 11 , further comprising about 1.0 mM to about 50 mM acetate. 
     
     
         13 . The pharmaceutical formulation of  claim 12 , contained in a glass vial or syringe, or a plastic vial or syringe. 
     
     
         14 . The formulation of  claim 13 , wherein the glass vial is a silicon dioxide coated glass vial. 
     
     
         15 . The formulation of  claim 14 , wherein the headspace in the glass vial is filled with an inert gas to remove oxygen. 
     
     
         16 . The formulation of  claim 15 , wherein the inert gas is argon or nitrogen. 
     
     
         17 . The pharmaceutical formulation of  claim 12 , contained in an autoinjector or microinfusor. 
     
     
         18 . The pharmaceutical formulation of  claim 13 , wherein the syringe comprises a fluorocarbon-coated plunger. 
     
     
         19 . The pharmaceutical formulation of  claim 18 , wherein the syringe is a low tungsten syringe. 
     
     
         20 . The pharmaceutical formulation of  claim 19 , wherein the syringe comprises a fluorocarbon-coated plunger. 
     
     
         21 . The pharmaceutical formulation of  claim 1 , wherein the human antibody that specifically binds to hNGF comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the HCVR comprises heavy chain complementarity determining regions comprising the amino acid sequences of SEQ ID NOs: 6, 8, and 10, and wherein the LCVR comprises light chain complementarity determining regions comprising the amino acid sequences of SEQ ID NOs: 14, 16 and 18. 
     
     
         22 . The pharmaceutical formulation of  claim 21 , wherein the human antibody that specifically binds to hNGF comprises heavy chain and light chain variable region (HCVR/LCVR) amino acid sequence pairs selected from the group consisting of: (i) SEQ ID NOs: 20/22; and (ii) SEQ ID NOs: 4/12. 
     
     
         23 . A pharmaceutical formulation comprising: (i) about 0.1-100 mg/mL of a human antibody that specifically binds to hNGF, wherein said antibody comprises a heavy chain and light chain variable region (HCVR/LCVR) amino acid sequence pair of SEQ ID NOs: 20/22; (ii) about 0.05% polysorbate 20; (iii) about 8% sucrose; and (iv) about 10 mM acetate. 
     
     
         24 . The pharmaceutical formulation of  claim 23 , wherein the pH of the formulation ranges from about 4.5 to 5.6. 
     
     
         25 . The pharmaceutical formulation of  claim 24 , wherein the pH of the formulation is 5.0. 
     
     
         26 . The pharmaceutical formulation of  claims 23 , wherein the formulation is administered intravenously or subcutaneously. 
     
     
         27 . A method of treating, preventing, or ameliorating at least one symptom of a disease or disorder associated with NGF activity or NGF activation, the method comprising administering a pharmaceutically effective amount of the pharmaceutical formulation of  claim 23 , with a pharmaceutically acceptable carrier.